Acellular embryoid body and hydroxybutyl chitosan composite hydrogels promote M2 macrophage polarization and accelerate diabetic cutaneous wound healing
Diabetic wound healing is delayed due to persistent inflammation, and macrophage-immunomodulating biomaterials can control the inflammatory phase and shorten the healing time. In this study, acellular embryoid bodies (aEBs) were prepared and mixed with thermosensitive hydroxybutyl chitosan (HBC) hyd...
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Elsevier
2024-04-01
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author | Yue Zhang Zheng-Hong Chen Kun Zhao Yu-Dong Mu Kun-Long Li Zhi-Min Yuan Zhi-Gang Liu Le Han Wei-Dong Lü |
author_facet | Yue Zhang Zheng-Hong Chen Kun Zhao Yu-Dong Mu Kun-Long Li Zhi-Min Yuan Zhi-Gang Liu Le Han Wei-Dong Lü |
author_sort | Yue Zhang |
collection | DOAJ |
description | Diabetic wound healing is delayed due to persistent inflammation, and macrophage-immunomodulating biomaterials can control the inflammatory phase and shorten the healing time. In this study, acellular embryoid bodies (aEBs) were prepared and mixed with thermosensitive hydroxybutyl chitosan (HBC) hydrogels to produce aEB/HBC composite hydrogels. The aEB/HBC composite hydrogels exhibited reversible temperature-sensitive phase transition behavior and a hybrid porous network. In vitro analysis showed that the aEB/HBC composite hydrogels exhibited better antimicrobial activity than the PBS control, aEBs or HBC hydrogels and promoted M0 to M2 polarization but not M1 to M2 macrophage repolarization in culture. The in vivo results showed that the aEB/HBC composite hydrogels accelerated cutaneous wound closure, re-epithelialization, ingrowth of new blood vessels, and collagen deposition and reduced the scar width during wound healing in diabetic mice over time. Macrophage phenotype analysis showed that the aEB/HBC composite hydrogels induce M2 macrophage reactions continually, upregulate M2-related mRNA and protein expression and downregulate M1-related mRNA and protein expression. Therefore, the aEB/HBC composite hydrogels have excellent antimicrobial activity, promote M2 macrophage polarization and accelerate the functional and structural healing of diabetic cutaneous wounds. |
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spelling | doaj.art-286d6c3c3d624f6cb28b251a525bd1b92024-03-18T04:34:20ZengElsevierMaterials Today Bio2590-00642024-04-0125100975Acellular embryoid body and hydroxybutyl chitosan composite hydrogels promote M2 macrophage polarization and accelerate diabetic cutaneous wound healingYue Zhang0Zheng-Hong Chen1Kun Zhao2Yu-Dong Mu3Kun-Long Li4Zhi-Min Yuan5Zhi-Gang Liu6Le Han7Wei-Dong Lü8Department of Pathophysiology, Northwestern University School of Life Sciences, Northwest University, Xi'an, Shaanxi, 710069, China; Key Laboratory of Resource Biology and Biotechnology in Western China, Ministry of Education, Northwest University, Xi'an, Shaanxi, 710069, ChinaOncology Department of Integrated Chinese and Western Medicine, Tumor Hospital of Shaanxi Province, Affiliated to the Medical College of Xi'an Jiaotong University, Xi'an, Shaanxi, 710061, ChinaDepartment of Thoracic Surgery, Tumor Hospital of Shaanxi Province, Affiliated to the Medical College of Xi'an Jiaotong University, Xi'an, Shaanxi, 710061, ChinaDepartment of Clinical Laboratory, Tumor Hospital of Shaanxi Province, Affiliated to the Medical College of Xi'an Jiaotong University, Xi'an, Shaanxi, 710061, ChinaDepartment of Thoracic Surgery, Tumor Hospital of Shaanxi Province, Affiliated to the Medical College of Xi'an Jiaotong University, Xi'an, Shaanxi, 710061, ChinaDepartment of Clinical Laboratory, Tumor Hospital of Shaanxi Province, Affiliated to the Medical College of Xi'an Jiaotong University, Xi'an, Shaanxi, 710061, ChinaDepartment of Thoracic Surgery, Tumor Hospital of Shaanxi Province, Affiliated to the Medical College of Xi'an Jiaotong University, Xi'an, Shaanxi, 710061, ChinaDepartment of Thoracic Surgery, Tumor Hospital of Shaanxi Province, Affiliated to the Medical College of Xi'an Jiaotong University, Xi'an, Shaanxi, 710061, ChinaDepartment of Thoracic Surgery, Tumor Hospital of Shaanxi Province, Affiliated to the Medical College of Xi'an Jiaotong University, Xi'an, Shaanxi, 710061, China; Corresponding author. Department of Thoracic Surgery, Tumor Hospital of Shaanxi Province, Affiliated to the Medical College of Xi'an Jiaotong University, 309 Yanta West Road, Xi'an, Shaanxi, 710061, China.Diabetic wound healing is delayed due to persistent inflammation, and macrophage-immunomodulating biomaterials can control the inflammatory phase and shorten the healing time. In this study, acellular embryoid bodies (aEBs) were prepared and mixed with thermosensitive hydroxybutyl chitosan (HBC) hydrogels to produce aEB/HBC composite hydrogels. The aEB/HBC composite hydrogels exhibited reversible temperature-sensitive phase transition behavior and a hybrid porous network. In vitro analysis showed that the aEB/HBC composite hydrogels exhibited better antimicrobial activity than the PBS control, aEBs or HBC hydrogels and promoted M0 to M2 polarization but not M1 to M2 macrophage repolarization in culture. The in vivo results showed that the aEB/HBC composite hydrogels accelerated cutaneous wound closure, re-epithelialization, ingrowth of new blood vessels, and collagen deposition and reduced the scar width during wound healing in diabetic mice over time. Macrophage phenotype analysis showed that the aEB/HBC composite hydrogels induce M2 macrophage reactions continually, upregulate M2-related mRNA and protein expression and downregulate M1-related mRNA and protein expression. Therefore, the aEB/HBC composite hydrogels have excellent antimicrobial activity, promote M2 macrophage polarization and accelerate the functional and structural healing of diabetic cutaneous wounds.http://www.sciencedirect.com/science/article/pii/S2590006424000346Acellular embryoid bodiesHydroxybutyl chitosanDiabetic wound healingMacrophage polarizationComposite hydrogels |
spellingShingle | Yue Zhang Zheng-Hong Chen Kun Zhao Yu-Dong Mu Kun-Long Li Zhi-Min Yuan Zhi-Gang Liu Le Han Wei-Dong Lü Acellular embryoid body and hydroxybutyl chitosan composite hydrogels promote M2 macrophage polarization and accelerate diabetic cutaneous wound healing Materials Today Bio Acellular embryoid bodies Hydroxybutyl chitosan Diabetic wound healing Macrophage polarization Composite hydrogels |
title | Acellular embryoid body and hydroxybutyl chitosan composite hydrogels promote M2 macrophage polarization and accelerate diabetic cutaneous wound healing |
title_full | Acellular embryoid body and hydroxybutyl chitosan composite hydrogels promote M2 macrophage polarization and accelerate diabetic cutaneous wound healing |
title_fullStr | Acellular embryoid body and hydroxybutyl chitosan composite hydrogels promote M2 macrophage polarization and accelerate diabetic cutaneous wound healing |
title_full_unstemmed | Acellular embryoid body and hydroxybutyl chitosan composite hydrogels promote M2 macrophage polarization and accelerate diabetic cutaneous wound healing |
title_short | Acellular embryoid body and hydroxybutyl chitosan composite hydrogels promote M2 macrophage polarization and accelerate diabetic cutaneous wound healing |
title_sort | acellular embryoid body and hydroxybutyl chitosan composite hydrogels promote m2 macrophage polarization and accelerate diabetic cutaneous wound healing |
topic | Acellular embryoid bodies Hydroxybutyl chitosan Diabetic wound healing Macrophage polarization Composite hydrogels |
url | http://www.sciencedirect.com/science/article/pii/S2590006424000346 |
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